The proposal is submitted by J. Stuart Nelson, M.D., Ph.D. for a K-24 Mid-Career Investigator Award in Patient Oriented Research. Dr. Nelson's M.D., Ph.D. training, academic affiliation, and involvement in the basic science and clinical applications of lasers make him uniquely qualified and experienced to pursue a career in patient oriented research. The requested protected time provided by this application will allow him the opportunity to maximize his time availability for the mentoring of young physicians interested in the emerging fields of photomedicine and biomedical optics. At least two fellows will be mentored at any given time. It is anticipated that 4-6 fellows will be mentored over the course of the proposed five years. The treatment success rate for the vast majority of port wine stain (PWS) patients is very low (< 10%) if the ultimate standard required is complete blanching of the lesion. The objective in the laser treatment of PWS is to maximize thermal damage to the targeted blood vessels while preventing injury to the normal overlying epidermis. Unfortunately, for many lesions, the threshold for epidermal damage is lower than that for permanent blanching of the PWS thereby precluding the use of higher and more effective laser light dosages. An important method to overcome the aforementioned problem is to cool selectively the most superficial layers of the skin. Although melanin absorption will result in heat production during laser exposure, cooling the epidermis can prevent its temperature from exceeding the threshold for thermal injury. Spatially selective cooling can be achieved by active cooling using cryogen spray cooling (CSQ. When a cryogen spurt is applied to the skin surface for an appropriately short period of time (tens of milliseconds), CSC promotes rapid and spatially selective epidermal cooling to low temperatures without affecting the targeted blood vessel temperature before the laser pulse is delivered. The successful development of CSC should. 1) improve therapeutic outcome; 2) reduce the number of treatment sessions; 3) shorten therapeutic protocols; and (4) improve safety. We intend to determine in comprehensive Phase 1, 11 and III clinical trials on PWS patients, the efficacy and safety of CSC in conjunction with laser treatment individualized for each patient; target enrollment is 225 subjects. We also propose to initiate several pilot studies on patients with pigmented dermatoses such as congenital hairy nevi, Becker's nevus, nevus spilus, blue nevus or nevi of Ota; target enrollment is 200 subjects.